PROJECT SUMMARY/ABSTRACT Bipolar disorder (BD) comorbid to substance use disorders (SUD) is linked to high rates of morbidity and mortality, increased frequency and severity of mood episodes, early onset of mood symptoms, poor role and cognitive functioning, and reduced quality of life, among other negative illness characteristics. Despite the significant illness burden carried by patients with these co-occurring conditions, existing treatments hold limited efficacy, suggesting the need for a re-consideration of mechanisms that may be impacting treatment outcomes in this population. Common to BD and SUDs are illness characteristics such as increased impulsivity, heightened novelty-seeking, and poor decision-making. Clinically, such characteristics are presented through high-risk tendencies such as excessive spending practices, HIV transmission risk behaviors (e.g., unprotected intercourse, needle sharing), and engagement with illegal activities, among other examples. Thus, one mechanism that may explain poor outcomes in patients with these co-occurring conditions is impaired risk avoidance, or a tendency to engage in a persistent pattern of behaviors despite poor outcomes resulting from such behaviors. The proposed study is focused on characterizing the nature and profile of laboratory-based risk avoidance deficits and determining the associations among risk avoidance, cognitive, and clinical risk behaviors to inform improved, focused, and novel intervention efforts across patient populations (NIMH Strategic Plan, 3.2). This study aims to 1) examine the profile of laboratory-derived risk avoidance impairments in those with BD with and without comorbid SUDs to inform future treatment advances for intervening with hazardous behaviors, and 2) investigate the association among monetary and fear-based laboratory risk avoidance assessments, cognitive assessments, and clinical risk behaviors to aid in formation of specific profiles of patients with comorbid BD and SUDs. Overall, the proposed project will enable the applicant to gain hands-on training with cognitive assessment and interpretation, fear conditioning, and psychophysiological data collection methods. Further, through this study, the applicant will 1) gain expertise in translational research methods, 2) enhance her knowledge base on historical and current research in the confluence of BD and SUDs (e.g., through coursework and readings), 3) receive training in empirically-supported psychosocial treatments for these co-occurring conditions, and 4) forge fruitful professional connections with researchers in the field who will collaborate with the applicant on future grant applications and thus allow her to achieve her translational science career goals. Patterns of laboratory-based risk avoidance, cognitive deficits, and clinical risk behaviors in this population will represent novel targets for treatment development that underlie mechanisms of comorbid BD and SUDs (NIMH Strategic Plan, 3.1). Thus, the proposed study represents an initial step towards improved, more effective treatments for co-occurring BD and SUDs.